Possible Evolutionary Advantage Seen in Breast Cancer Genes

Possible Evolutionary Advantage Seen in Breast Cancer Genes

SEATTLE--"Is it possible that at some point in human evolution,
there was some selective advantage of BRCA1 and BRCA2?" Mary-Claire
King, PhD, asked during her presentation at the annual meeting of the American
Association for the Advancement of Science (AAAS).

These breast cancer genes may have offered a very important evolutionary
advantage--increased lactation--suggested Dr. King, professor of medicine
and genetics, University of Washington.

Dr. King noted that the normal copy of the gene works to control cell
proliferation in the breasts, ovaries, and prostate. A mutation that knocked
out that control could increase lactation, among other consequences.

For societies living on subsistence diets, "anything that stimulates
lactation would be a benefit," she said. This potential advantage
of old, however, "has no meaning for the young woman in the modern
era."

While inherited BRCA1 and BRCA2 mutations cause only a small fraction
of breast cancers, they offer important opportunities to further understand
the genetics of cancer in both sexes.

Dr. King described one BRCA2 family in which breast cancer struck the
female members often, as one would expect. But five males in the family
also developed the disease, quite evidently from inheriting the gene.

She also noted increasing evidence that the two breast cancer genes
can be a cause of prostate cancer, with BRCA2 probably playing a bigger
role.

A True Tale of Genetic Testing

In her AAAS presentation, Dr. King described two women from a hereditary
breast cancer family that she has been studying for many years.

The two sisters had prophylactic mastectomies more than 10 years ago,
well before the discovery of BRCA1 and the development of a test for the
gene.

It fell to Dr. King to eventually tell each sister that she had not
inherited the family's cancer gene. Somewhat to her surprise, the first
response from both women was: "Thank God, I don't have to worry about
my daughter." And both women felt they had made a rational decision
in having their breasts removed, given the information available to them
at the time

A recent discovery related to colon cancer has pointed a new direction
for breast cancer genetics, Dr. King said. People with the APC gene, a
gene linked to inherited colon cancer, do not all suffer disease of identical
severity, nor do mice who inherit a similar gene.

Researchers working with mice discovered that a second gene acts to
modify the effect of the APC gene. A counterpart to the mouse modifier
gene has now been identified in humans.

"We're not at that point in breast cancer yet, but some day we
will be," Dr. King predicted.

Gene Therapy

At the same AAAS session, in a presentation on gene therapy, Mark A.
Kay, MD, PhD, of the University of Washington, noted that the emphasis
has moved from experimental treatments of single-gene inherited diseases
to trials for such common illnesses as cancer, heart disease, and diabetes.
Of some 150 gene therapy trials to date, most have targeted "nongenetic"
diseases, he said. The shift largely stems from the pharmaceutical industry's
expanding interest in diseases with greater market value, he said, with
cancer an important target.

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